The goal of this research is to elucidate the stereochemistry of drug-nucleic acid interactions and to understand the mechanisms of drug action of a wide spectrum of drugs and antibiotics which exert their pharmacological action by binding to nucleic acids (DNA and RNA). This research proposal describes efforts on applying the physico-chemical techniques such as molecular co-crystallization, X-ray diffraction, and spectroscopic techniques to the studies of the interaction of nucleic acids with anticancer drugs and antiviral agents (such as antiviral drugs and interferon inducers tilorone and its derivatives). The results of these studies may provide useful information for the rational design of more effective anticancer drugs, antiviral agents and interferon inducers. Highlights of current research: Co-crystallization of tilorone and its derivative (DEAP-fluoranthene) with various complementary dinucleoside monophosphates has been successful. Co-crystallization of ethidium bromide with deoxydinucleoside monophosphates has been successful. X-ray crystallographic studies of some of these crystals are in progress.